WD40编码的P53 RNA反义转录子基因和蛋白及其功能

The function of the WD40-encoding RNA antisense to P53 and protein

WD40编码的P53 RNA反义转录子(WRAP53)基因有1α、1β和1γ三个起始外显子,1α与P53的第一外显子反向互补,其表达产物能稳定P53 RNA水平,从而促进P53蛋白表达,最终参与调控肿瘤的生物学行为;1β转录翻译生成的WRAP53蛋白,涉及细胞程序性死亡、周期调控以及蛋白酶降解和RNA代谢等多个重要生化过程。WRAP53蛋白主要通过与端粒酶复合体等多种组分结合参与端粒酶卡侯体(CB)的形成、端粒酶全酶的组装定位、端粒酶的运输,指导运动神经元生存蛋白定位至CB等。WRAP53基因在肿瘤细胞系和临床肿瘤样本中普遍高表达,且表达越高,肿瘤的预后越差。沉默WRAP53基因,可明显抑制肿瘤细胞的生长和成瘤能力。先天性角化不良综合征与端粒长度的缩短有关,WRAP53基因表达降低最终会导致端粒的缩短。

WD40-encoding RNA antisense to P53 has three exons： 1α, 1β, and 17. The exon la of WRAP53 directly overlaps the first exon of P53 in an antisense way. The WRAP53 1α transcript could regulate the level of P53 RNA, and then induce the expression of the P53 protein. The biological behavior of tumor could be regulated by P53 protein. The exon 1β of WRAP53 produces a protein called WRAP53 protein, which is associated with programmed cell death, cycle regulation, protease degradation and RNA metabolism. WRAP53 protein contacts with various components of telomerase, helps the telomerase to locate in Cajal body（CB） and is an essential factor for CB formation, maintenance and the location of survival motor neuron. WRAP53 has a high expression in tumor cell and clinical tumor sample. The higher the expression of WRAP53 is, the worse of the prognosis of tumor will be. Silencing the WRAP53 can inhibit the growth of tumor cell. Dyskeratosis congenital is related to the shortage of the length of telomere which is owing to the low expression of WRAP53.